Cancer is a major threat to human health, and a majority of cancers in human are caused by external environmental factors. Every year at least 5 million persons died of cancer around the world. The cure rate is still low although some treatment methods of cancers are currently available to cure patients, such as surgery, radiotherapy, chemotherapy and so on. Using chemical pharmaceuticals for preventing and treating cancers is currently one of the most effective methods.
Thienopyridazine compounds or compounds of their thieno analogues have been found to have anti-tumor activities.
F. Hoffman-La Roche AG discloses a thienopyridazine as an IKK inhibitor in WO2005105808.
Amgen Inc. of USA discloses a thienopyridazine compound as a p38 protease inhibitor of tyrosine kinase in WO2007124181.

Smithkline Beecham Corporation discloses a 2-ureidothiophene compound in WO03029241 and a 3-ureidothiophene compound in WO03028731, which are similar to thienopyridazine compounds as CHK1 inhibitors. AstraZeneca AB discloses a 3-ureidothiophene modified compound as a CHK1 inhibitor in WO 2005066163.
Chemical pharmaceuticals for preventing and treating cancers currently include inhibitors of receptors of tyrosine kinases and non-receptors of tyrosine kinases, and their targets include VEGFR, EGFR, HER2, SRC, JAK and TEK; and also include inhibitors of threonine-serine kinases and their targets include MEK, JNK, c-MET, AKT, PIM, TIE, PLK and so on. The compounds of the present invention are inhibitors of cancers and protein kinases including Checkpoint Kinase CHK1/CHK2 of cell cycles.
It has been found from researches for regulations of checkpoints of cell cycle that closing expression of CHK1 can reverse drug resistance of cancer cells, thereby increase sensitivities of tumor cells to DNA damage therapy, and dramatically increase activities of anti-cancer pharmaceuticals. In addition, it may obtain tumors selective pharmaceuticals through majorities of tumors having mutations features in p53 of eliminating G1/S checkpoint. The present invention provides a novel thienopyridazine compound as inhibitors of protein kinases of novel tumors associated with growth factors (including CHK1, CHK2), which not only have anti-tumor actions but also can enhance anti-tumor effectiveness of other anti-tumor pharmaceuticals.